The cover layers used in conventional transdermal therapeutic systems are films made from acetal, acrylate, acrylonitrile butadiene styrene, acrylonitrile (methyl methacrylate) copolymer, acrylonitrile copolymer, ethylene ethyl acrylate, ethylene methyl acrylate, ethylene vinyl acetate, ethylene vinyl acetate copolymer, ethylene vinyl alcohol polymer, ionomers, nylon (polyamide), nylon copolymer, polybutylene, polycarbonate, polyester, polyethylene terephthalate, thermoplastic polyester copolymer, polyethylene copolymer (high-density), polyethylene (high molecular weight, high-density), polyethylene (intermediate molecular weight, high-density), polyethylene (linear low-density), polyethylene (low density), polyethylene (medium density), polyethylene oxide, polyimide, polypropylene, polypropylene (coated), polypropylene (oriented), polystyrene, polyurethane, polyvinyl acetate, polyvinyl chloride, polyvinylidene chloride, and/or styrene acrylonitrile, which, if required, may have been metallized or pigmented. They serve to stabilize the active substance-containing system and protect it against external influences. The cover layer is impermeable to the active substances and therefore prevents the active substance from diffusing to the outside.
The removable protective layers that are used in transdermal therapeutic systems are also impermeable to the active substances and are usually made from polyester, polyethylene, polypropylene, polysiloxane, polyacrylate, ethylene vinyl acetate, polyurethane, polyisobutene or paper, in most cases coated with silicon and/or polyethylene, or a composite of these. They also serve to stabilize the active substance-containing system and protect it against external influences. The removable protective layer is impermeable to the active substances and therefore prevents the active substance from diffusing to the outside during storage.
Transdermal therapeutic systems are usually packaged in sachets. The sachets are usually made from a laminate material coated with aluminum. Such coating increases the impermeability to humidity and oxygen of the packaging. Permeability depends on the thickness of the coating. As the thickness of the aluminum coating increases, environmental incompatibility and the costs incurred in manufacturing and disposing of the packaging increases. In practice, however, total impermeability can not be attained. For that reason, the transdermal therapeutic system is always exposed to a certain degree of humidity. In addition, after production, the transdermal therapeutic system releases a certain amount of residual humidity to the environment. To ensure suitable storage stability, in the sachet, an inlay can be placed which contains a drying agent. As a result, however, the packaging of the transdermal therapeutic system becomes more complicated and significantly more expensive. Highly odorous substances such as amines and polymer monomers which are released during storage from the active substance or the pressure-sensitive adhesive layer can not be eliminated at all or only partially by using this method.
The object of this present invention is to increase the storage stability of transdermal therapeutic systems by minimizing the negative impact of humidity, oxygen, free amines and/or free polymer monomers on the stability of the transdermal therapeutic systems. At the same time, the transdermal therapeutic systems are to be manufactured by conventional means, without any complicated additional production steps, and packaging costs are to be reduced simultaneously.
Surprisingly, it has been possible to achieve the object of this present invention by using, as a cover layer that is impermeable to the active substances or as a removable protective layer of the transdermal therapeutic system, a polymer in the form of a film which either directly contains the absorbing agents and channel-forming agents or which is coated with a polymer support containing these substances. The coating can be applied either over the entire surface of the film or in patterns (e.g. in a grid pattern) directly during production.
The company Capitol Specialty Plastics holds several patent applications (WO 00/17259, WO 00/17260, WO 00/16884, WO 99/62697, WO 99/61856, WO 98/39231, WO 99/61855, WO 00/17258, WO 99/63288, U.S. Pat. No. 5,911,937) which claim polymers containing absorbing agents, releasing agents, channel-forming agents, etc. These polymers are mainly used to eliminate humidity from packages. They are either inlays that are placed in the packages, or the packages are lined therewith. The thickness of the inlays and coating films described is ≧400 μm. This is disadvantageous insofar as these inlays or coatings require an additional production step and represent another cost factor.
By using the cover layer and/or removable protective layer in accordance with this present invention, the thickness of the aluminum coating of the packaging can be greatly reduced. This benefits the environment and reduces the costs of the packaging. The manufacturing process need not be changed. Common state-of-the-art manufacturing processes can continue to be used. In addition, no additional drying element needs to be placed in the packaging. The manufacturing costs of the TTS can therefore be significantly reduced.